The ABC of clinical and experimental adjuvants--a brief overview

Abstract

Adjuvants are compounds that can increase and/or modulate the intrinsic immunogenicity of an antigen and elicit strong and long lasting immune responses. During the last 80 years many adjuvants have been used in experimental settings, but due to various shortcomings of most of them only aluminum compounds made it into regular clinical usage. However, during the last years promising candidates have arisen that may finally adjunct or displace aluminum substances as main adjuvant. This review summarizes information on adjuvants currently used in clinical as well as in experimental settings.

Fig. 1

Mechanisms of adjuvants. The initiation of Th cell responses requires three signals, referred to as signal 0, signal 1 and signal 2. In theory, adjuvants can act on each of these three signals. Most of the recently developed specific adjuvants, such as Toll-like receptor (TLR) agonists, are called type A adjuvants (e.g. MPL). Adjuvants and formulations targeting antigen processing cells (APCs) or favoring antigen capture are called type B adjuvants (e.g. aluminum hydroxide), acting on signal 1, as their effect is mediated by enhanced antigen presentation to T cells. Specific ligands of co-stimulatory molecules, like the CD28 agonist TGN1412, can enhance signal 2 and are called type C adjuvants. Signal 3 represents mediators delivered from the APC to the T cell, e.g. the cytokine IL-12.

Fig. 2

Cholera toxin. (A) Cholera toxin consists of the two main subunits, cholera toxin A subunit (CTA) and cholera toxin B subunit (CTB). CTB is accountable for the adjuvant capabilities, while CTA’s toxicity causes severe gastrointestinal symptoms. (B) Thus, during production of vaccines/adjuvants, CTA is cleaved off and CTB is linked to the antigen of choice. (C) CTB binds to the GM-1 receptor on enterocytes and enhances recognition of the linked antigen by the immune system.